Factors affecting the rate of reaction of platinum(II) complexes with DNA and protein targets

NMR spectroscopy has been used to observe the effects of ligand bulk and hydrogen bonding on the rates of reaction of platinum complexes with DNA and protein residues. The reactions of [Pt(dien)(D2O)]2+ (dien = diethylenetriamine) or [Pt(Me4en)(D2O)2]2+ (Me4en = N, N, N',N'-tetramethylethylenediamine) with 5'GMP (guanosine 5' monophosphate) and/or N-AcMet (N-acetylmethionine) have been monitored by NMR spectroscopy. We have determined rate constants and utilized kinetic competition experiments in which a platinum complex has been added to 5'-GMP and/or N-AcMet. It was observed that [Pt(dien)(D2O)]2+ reacted faster with N-AcMet than with 5'-GMP, whereas [Pt(Me4en)(D2O)2]2+ had a tendency to react faster with 5'-GMP than with N-AcMet. We are now utilizing experiments with [Pt(en)(D2O)2]2+ as well as experiments with guanosine to determine whether the preference for 5'-GMP is related to amine ligand bulk or to hydrogen bonding.